Research into new therapeutic strategies for the treatment of pediatric solid tumors is focused on bone and soft-tissue sarcomas including Ewing's sarcoma, peripheral neuroepithelioma, rhabdomyosarcoma and osteosarcoma as well as neuroblastoma and malignant brain tumors. These common pediatric tumors remain diagnostic and therapeutic challenges for which new approaches are needed. The sarcomas serve as an excellent "model system" for the exploration of strategies and hypotheses that have broad applicability to both pediatric and adult solid tumor oncology. The overall goal of these protocols is to learn how to us drugs that have been determined to be active in the pediatric sarcomas with sufficient intensity to maximize their therapeutic potential. Previous Pediatric Branch protocols have demonstrated a very high response rate for intensive vincristine, adriamycin and cyclophosphamide in newly diagnosed sarcoma patients (83-C-73) and a high level of activity for ifosfamide, mesna and etoposide in those with recurrent tumors (85-C-154). The current front-line sarcoma protocol (86-C-169) is studying the integration of the ifosfamide, mesna, etoposide combination with intensive vincristine, adriamycin, cyclophosphamide, local irradiation. In an effort to circumvent the major toxicity associated with this protocol, myelosuppression, we are studying the hematopoietic growth factor rh-GM-CSF in a randomized trial to determine whether its use will decrease the myelosuppression, related delays and toxicity (88-C-165). We are also studying the iron chelator ICRF-187 in a randomized trial (89-C-07) in patients on the sarcoma protocol to learn whether it will protect the heart from adriamycin induced myocardial damage. These studies of ICRF-187 and rh-GM-CSF are unique in that they are the only ongoing front-line trials of these promising new approaches in pediatric solid tumor patients. These studies are nearing completion. Subsequent studies will assess the activity of new agents in the pediatric solid tumors in a phase II "window" design.